1. Field of the Invention
The present invention relates generally to methods and apparatus for combining parenteral solutions. More particularly, the present invention relates to methods for combining sodium bicarbonate and other buffering solutions with parenteral solutions stored in small cartridges.
Solutions containing bicarbonate ions are used in various medical applications such as antidotes, dialysates, artificial cerebrospinal fluid, intraocular irrigating solutions, cardiac perfusates, cardioplegic solutions, peritoneal irrigating solutions, and solutions for organ preservation, etc. Of particular interest to the present application bicarbonate solutions are used to buffer the pH dental anesthetic and other parenteral solutions. One of the most commonly used medical bicarbonate solutions consists of sodium bicarbonate (NaHCO3) mixed with water (H2O). In medical bicarbonate solutions, bicarbonate ions are in equilibrium as represented by the following expression:2HCO3−CO2↑+CO32−+H2O
If the reaction occurs in a closed system, equilibrium is between the partial pressure of carbon dioxide in solution and the partial pressure of carbon dioxide in any space over the solution. In open systems at atmospheric pressure and room temperature, for instance where a beaker of sodium bicarbonate solution is left open in a lab environment, carbon dioxide gas will continue to leave solution until the reaction has proceeded almost completely to the right, or until almost all the bicarbonate (2HCO3) has evolved into carbon dioxide gas (CO2), carbonate (CO3) and water (H2O), and where all the CO2 gas has left the open beaker and entered the ambient air in the lab. Bicarbonate is more acid than carbonate, meaning that the pH of the solution will have progressively moved toward the alkaline side of the pH scale. In fact, under these circumstances, the bicarbonate solution will achieve a pH over 9.5.
All commercially available medical sodium bicarbonate solutions are supplied sterile in closed containers. All of them also have some amount of headspace into which, presumably, CO2 could evolve out of solution until an equilibrium between CO2 evolving out of solution and going back in to solution, per the above equation, is reached. It could therefore be hypothesized that the commercially available sodium bicarbonate solutions have a pH that could exist in a fairly wide range. In fact the labels on all commercially available medical bicarbonate solutions state, per the United States Pharmacopeia guidelines, that the pH can be anywhere from 7.0 to 8.5. An assay of a sample set of commercially available medical sodium bicarbonate solutions in a variety of volumes and containers may have pH range from 7.6 to 8.3 or more.
The pH of bicarbonate solutions is thus not a fixed figure, but rather can exist at a range of levels dictated by the factors that tend to push the equilibrium equation, in a particular environment, either to the right or to the left, principally controlled by CO2 leaving or entering solution.
Notably, in a closed container with no headspace, the pH of sodium bicarbonate solution can be fixed by placing the solution having a known starting pH, in a sealed container under pressure that exceeds the partial pressure of CO2 in the solution, without a headspace. In that environment, CO2 will not evolve out of solution because pressure on the solution is greater than the partial pressure of CO2, and therefore the pH will not rise. Also in this environment where the pressure being exerted on the solution is greater than the partial pressure of CO2 in solution, because there is no headspace, and hence no available CO2 gas that can be driven into solution, the pH of the solution will not decrease. In this model then, CO2 does not leave or enter solution and, accordingly, the pH does not have the opportunity to either rise or fall. The pH of the solution in this system, is therefore, essentially fixed once the system is closed.
Even if the pH is known and fixed within a sealed container, a significant pH change can be caused by the process of transferring the bicarbonate solution out of the container. Where the bicarbonate solution is to be combined with another solution, as in anesthetic buffering, the process of mixing two solutions together can also include steps that will create a greater or lesser pH change, which can affect the predictability of the buffering process.
These considerations are important in buffering parenteral solutions using a syringe with a hypodermic needle to “draw up” bicarbonate solution from a vial having a pierceable septum, and then mixing the bicarbonate with the target solution in order to alter the pH of the target solution. This vial and syringe system is typical and allows a practitioner to remove multiple doses of solution from a container without opening the container or exposing it to the ambient air. Vials that are intended to be used in this manner necessarily include a significant headspace, without which drawing up fluid in this manner could not occur. When the vial contains a headspace, as the practitioner withdraws the syringe's plunger, the headspace can expand to fill the space vacated by the liquid that is leaving the vial, traveling through the hypodermic needle, and entering the barrel of the syringe. Of course, as more and more solution is drawn up, for instance as multiple doses of the solution are used, the headspace expands more and more, continually lowering the gas pressure in that headspace.
Where a vial of this type contains bicarbonate that is removed in doses using a syringe, over time, because the partial pressure of the gas in the headspace drops, the partial pressure of CO2 in the headspace drops as well, taking it out of equilibrium with the partial pressure of the CO2 in solution. Per the equation set forth earlier, CO2 gas will evolve out of solution to re-establish the equilibrium, which has the effect of raising the pH of the bicarbonate solution each time a volume of the solution is drawn up into a syringe. Whatever the starting pH of the vial's bicarbonate solution may have been, if it were known, the pH of the solution in the vial, after any amount of the solution has been removed in this manner, cannot be known. Therefore, if the pH of the solution is an important element of its clinical utility, as when the bicarbonate is to be used for buffering the pH of a target solution such as anesthetic, withdrawing bicarbonate from a vial using a syringe may alter the pH to a degree that makes it difficult to predictably buffer any parenteral solution using this method.
Another concern when bicarbonate solution is drawn from a vial using a syringe is the effect of the vacuum created in the fluid path that leads from the bicarbonate vial to the syringe. It has been observed that it is nearly impossible to draw up solution from a vial into a syringe using a needle in the range typically employed for injections (25-30 gauge) without creating gas in the syringe during the process. This is because the act of drawing the solution into the syringe creates a vacuum on that solution that causes significant CO2 to evolve out of the solution that is being transferred. The resulting pH change, along with the pH change that is occurring inside the vial with every withdrawal of a dose of bicarbonate from the vial itself means that it is impossible to know what the pH of the bicarbonate solution being used as a buffer is. With that lack of knowledge, the practitioner cannot control for the key variable that would inform him or her as to how much bicarbonate solution should be used in the buffering process. For this reason, buffering anesthetic using a vial of bicarbonate and a hypodermic syringe is akin to a “home brew” where the results are not predictable and, in the case where the pH of the bicarbonate is too high, could buffer the anesthetic into a range where it can precipitate out of solution, making the buffered anesthetic dangerous.
Commonly-owned copending application US 2009/0292271 (application Ser. No. 12/406,670, previously incorporated herein by reference) describes a “dosing pen” device capable of combining buffers and anesthetics and overcoming many of the shortcomings of the prior art described above. The '271 application discloses a fluid transfer device which utilizes a transfer needle 36 and an exhaust needle 38 positioned in a knob 12 which can removably receive an anesthetic cartridge 28 so that distal ends of both the transfer needle and exhaust needle penetrate a septum on the anesthetic cartridge. A buffer cartridge 16 positioned within a housing 14 is also attached to the knob 12 so that a proximal end 50 of the transfer needle 36 can penetrate a septum 15 of the buffer cartridge when the knob is fully advanced onto the housing. A pusher 20 is provided to drive a plunger 58 on the buffer cartridge to transfer buffer through transfer needle 36 into the anesthetic cartridge 28 and to simultaneously exhaust anesthetic from the anesthetic cartridge back into a reservoir 72 in the housing 14 through the exhaust needle 38.
While the dosing pen of the '271 application is advantageous in many respects, some improvements can be made such that a similar pen will provide additional benefits. First, the dosing pen is designed to hold a single buffer cartridge 16, and the design of the pen makes it difficult to replace the buffer cartridge. In particular, the pusher 20 is attached to the housing 14 to position an intermediate spring 18 against the plunger of the buffer cartridge, and a mechanism is provided which defines two advancement strokes to allow transfer of two pre-defined volumes of buffer to one or two anesthetic cartridges. The pusher assembly is not easily disassembled, making replacement of the buffer difficult. Thus, the entire pen must be disposed of after use.
Second, the pusher mechanism described above does not allow free selection of a range of transfer volumes prior to use. The pusher mechanism only allows two pre-defined volumes to be transferred by any particular pen construction. It would be desirable to allow a user to select or “dial in” any volume in a given range without being limited to specific preset values.
Third, the excess buffer, which is exhausted through exhaust needle 38, ends up in the housing 14. While it is theoretically possible to empty the buffer and clean the housing (assuming the device could be disassembled, which is difficult), it would be preferable if the excess buffer were exhausted into another component of the system which could either be more easily cleaned or be disposed of while allowing other components to be reused.
Fourth, removal of the first buffer cartridge from the dosing pen of the '271 application can be done without having removed the transfer needle from the buffer cartridge. Having a needle that can be left in a position where it provides a fluid path open to the ambient air (that is penetrating the septum of the buffer cartridge) could allow carbon dioxide to evolve out of solution, thus potentially affecting the pH of the buffer.
For these reasons, it would be desirable to provide improved methods and apparatus for combining buffer solutions with anesthetics, particularly where the buffer solutions and/or anesthetics are held in conventional glass cartridges with needle penetrable septums and dispensing plungers. It would be further desirable if such methods and apparatus could be used with other parenteral and medical solutions which are desired to be combined under carefully controlled conditions. The methods and devices would preferably allow for convenient buffering or dosing of multiple anesthetic or other cartridges from a single buffer or other medical solution cartridge. It would be still further desirable if the methods and devices provided for a removal of a transfer needle from the buffer or other medical solution cartridge every time the anesthetic or other recipient cartridge was removed from the dosing apparatus. Still further, it would be desirable if some components of the apparatus were reusable and the buffer cartridges replaceable. At least some of these objectives will be met by the inventions described hereinbelow.
2. Description of the Background Art
US2009/0292271 has been described above. Glass vials and cartridges for storing medical solutions are described in U.S. Pat. Nos. 1,757,809; 2,484,657; 4,259,956; 5,062,832; 5,137,528; 5,149,320; 5,226,901; 5,330,426; and 6,022,337. Injection pens which employ drug cartridges are described in U.S. Pat. No. 5,984,906. A particular disposable drug cartridge that can find use in the present invention is described in U.S. Pat. No. 5,603,695. A device for delivering a buffering agent into an anesthetic cartridge using a transfer needle is described in U.S. Pat. No. 5,603,695. Devices for maintaining a dissolved gas in solution in a pouch are described in U.S. Pat. Nos. 5,690,215; 5,610,170; and 4,513,015, and U.S. Patent Publ. No. 2007/0265593. Other patents and applications of interest include U.S. Pat. Nos. 2,604,095; 3,993,791; 4,154,820; 4,630,727; 4,654,204; 4,756,838; 4,959,175; 5,296,242; 5,383,324; 5,603,695; 5,609,838; 5,779,357; and U.S. Patent Publ. No. 2004/0175437.